In recent years, a variety of medical equipment, for example, artificial blood vessels, blood vessel catheters, tubes for artificial kidney, artificial hearts and lung, blood bypath tubes, etc., have become widely used in various manners in which they are brought into direct contact with blood.
These medical equipments used at regions which are brought into direct contact with blood are required to have not only a good elasticity, durability, wet strength, etc., but also are required to be excellent particularly in an antithrombogenic property and compatibility with a living body.
Accordingly, polymers such as nylons, polyesters, polyethylene, polypropylene, polyurethane, fluorine resins, etc. to which an antithrombogenic property and a compatibility with a living body have been imparted are used as materials of such medical equipment.
As a method for imparting an antithrombogenic property to the polymers described above, there have been hitherto known in the art a method in which the materials per se are modified to be those resistant to thrombus formation, a method which comprises incorporating or binding with chemical bonds a natural anticoagulant such as heparin to the materials, a method which comprises coating, e.g., collagen having excellent compatibility with a living body on the surface of the materials, and the like.
Among the methods noted above, examples of the method in which a material per se is modified to be resistant to thrombus formation include a certain polyurethane compound having such a structure that hydrophobic and hydrophilic portions appear on the surface thereof alternately (as described in U.S. Pat. Nos. 4,242,474 and 4,465,480); and a base polymer having bound thereto a hydrogel or a hydrophilic polymer (as described in Japanese Patent Application (OPI) No. 22926/85) (the term "OPI" used herein means published unexamined patent application). However, these polymers are still not totally satisfactory for practical use, although these materials do show a considerably high antithrombogenic property, and thus fully satisfactory materials have not yet been obtained.
Examples of the method for chemically binding a natural anticoagulant such as heparin to the material include a method which comprises graft polymerizing a vinyl compound having a tertiary amino group to a base polymer, quaternizing the amino group in the grafted polymer, and then heparinizing the same (as described in Japanese Patent Applicaiton (OPI) Nos. 206753/83 and 31868/82). However, the thus heparinized polymer is defective in that desired dynamic strength inherent to the base polymer is reduced, and strength and durability necessary for practical use cannot be obtained.
Furthermore, examples of the method which comprises, e.g., coating collagen onto the surface of the material include a method which comprises subjecting the surface of polyethylene, polypropylene, polyester, etc. to a polarization treatment, e.g., a treatment with chromic acid or an alkali, to render the surface hydrophilic, coating collagen onto the surface, and irradiating to effect binding of the coated collagen (as described in Japanese Patent Publication No. 37433/71), and a method which comprises subjecting the surface of a silicone rubber material to a polarization treatment such as plasma glow discharge treatment, a chemical treatment, etc., to render the surface hydrophilic, and then coating collagen in a manner as described above (as described in Japanese Patent Publication No. 4559/74). However, even the thus collagen-coated polymers provide only an insufficient antithrombogenic property and are not necessarily satisfactory for clinical applicaiton.
On the other hand, those using living materials themselves such as collagen (e.g., a tube made of collagen per se as described in European Patent Application 83302178A and 83302077A, and a porous substrate having provided thereon collagen as described in British Patents 2,153,235 and 2,153,685) have excellent compatibility with a living body as compared to the aforesaid polymers, but still encounter a problem with respect to antithrombogenic property.
As such, materials suited for clinical application which are sufficiently satisfactory with respect to both an antithrombogenic property and compatibility with a living body have not been yet found heretofore; particularly with respect to artificial blood vessels having an inner diameter of from 1 to 3 mm, it is the actual situation that materials which can fully prevent thrombus formation suddenly caused after transplantation have not yet been developed.
The present inventors have made extensive investigations to obtain materials suitable for clinical application having an excellent antithrombogenic property and compatibility with a living body, and previously developed polymers having bound mucopolysaccharides to the surface thereof activated by a plasma glow discharge treatment (as described in Japanese Patent Application (OPI) No. 183762/84), polymers having provided a collagen layer on the surface thereof and further provided thereon a heparin layer via a layer of fibronectin known as a cell adhesive protein (as described in Japanese Patent Application (OPI) No. 190966/85), and polymers having laminated thereon a layer of a mixture of an antithrombogenic mucopolysaccharides and collagen from which antigenic groups have been removed, or a gelatinized product thereof on the surface of the materials followed by crosslinking with a polyvalent aldehyde compound (as described in Japanese Patent Application (OPI) No. 191364/86).
However, these antithrombogenic materials are still insufficient to fully satisfy both the desired antithrombogenic property and compatibility with a living body at the same time, although they are improved to a considerable degree as compared to earlier materials. Thus, further improved materials are necessary.